Transplant Trial Watch

Unexpected CMV replication kinetics in CMV- donor seropositive recipient seronegative liver transplant recipients receiving preemptive antiviral therapy.

Singh, N., et al.

Journal of Infectious Diseases 2021 [record in progress].


Aims
This is a sub-study of a randomised controlled trial (RCT) comparing preemptive therapy (PET) versus antiviral prophylaxis in seropositive donor and seronegative recipient (D+R−) liver transplant recipients for the prevention of cytomegalovirus (CMV) infection. The aim of this study was to investigate the CMV replication kinetics in D+R- liver transplant recipients that were included in the PET arm of the original RCT.

Interventions
Participants in the original RCT were randomised to either the preemptive therapy group or the antiviral prophylaxis group.

Participants
79 (D+R−) liver transplant recipients receiving preemptive antiviral therapy.

Outcomes
The main outcomes of interest were recurrent viremia, CMV infection, opportunistic infections and allograft rejection (biopsy-proven).

Follow-up
12 months

CET Conclusions
This is an interesting paper that documents CMV replication after pre-emptive therapy in D+R- liver transplantation. It is a post-hoc analysis of the results from one arm in a randomised controlled trial that has previously been published (Singh et al, JAMA 2020: 323(14):1378-1387). Valganciclovir 900mg twice daily was used as pre-emptive therapy when viraemia was detected at any level and continued until two consecutive tests one week apart were negative. Viral load measurements were taken over a 100 day study period. 79 patients were eligible for the study and had a median of 14 blood samples each for analysis. The median time to first detection of viraemia was 21 days post-transplant and initial viral load was median 120 IU/ml. Pre-emptive therapy was initiated a median of 2 days after the onset of viraemia. Viral load increased over 10,000 IU/ml in over 25% of patients. Over 93% of patients had a median 1.1 log10 increase in viral load from baseline to peak level after starting pre-emptive therapy, and this peak came a median 14 days after starting treatment. The initial baseline viral load was not significantly different for patients with or without high level in increase in viral load after starting treatment. 55% had recurrent viraemia during the first 100 days and this was less likely in patients who had a high-level increase in viral load during the first peak. There were no demographic or immunosuppressive factors associated with high level increase, although the study may have been too small to identify these. CMV-resistance was not tested, however the viraemia resolved with valganciclovir treatment and this study demonstrates the probable dynamic of CMV infection: An increase in viral load can be expected for 14 days after initiation of therapy and does not warrant testing for CMV resistance. The mechanisms are not fully understood.

Trial registration
ClinicalTrials.gov - NCT01552369

Funding source
Non-industry funded